Altered limbic functional connectivity in individuals with subjective cognitive decline: Converging and diverging findings across Chinese and German cohorts

Abstract

INTRODUCTIONIt remains unclear whether functional brain networks are consistently altered in individuals with subjective cognitive decline (SCD) of diverse ethnic and cultural backgrounds and whether the network alterations are associated with an amyloid burden.METHODSCross‐sectional resting‐state functional magnetic resonance imaging connectivity (FC) and amyloid‐positron emission tomography (PET) data from the Chinese Sino Longitudinal Study on Cognitive Decline and German DZNE Longitudinal Cognitive Impairment and Dementia cohorts were analyzed.RESULTSLimbic FC, particularly hippocampal connectivity with right insula, was consistently higher in SCD than in controls, and correlated with SCD‐plus features. Smaller SCD subcohorts with PET showed inconsistent amyloid positivity rates and FC–amyloid associations across cohorts.DISCUSSIONOur results suggest an early adaptation of the limbic network in SCD, which may reflect increased awareness of cognitive decline, irrespective of amyloid pathology. Different amyloid positivity rates may indicate a heterogeneous underlying etiology in Eastern and Western SCD cohorts when applying current research criteria. Future studies should identify culture‐specific features to enrich preclinical Alzheimer's disease in non‐Western populations.Highlights Common limbic hyperconnectivity across Chinese and German subjective cognitive decline (SCD) cohorts was observed. Limbic hyperconnectivity may reflect awareness of cognition, irrespective of amyloid load. Further cross‐cultural harmonization of SCD regarding Alzheimer's disease pathology is required.

The preservation of right cingulum fibers in subjective cognitive decline of preclinical phase of Alzheimer’s disease

“…However, our results revealed subtle increases in white matter changes in the preclinical stage of AD that were not detectable using conventional MRI, suggesting an innovative compensation mechanism in the early course of AD. A recently published study that included data from two large, independent, ongoing longitudinal observational studies showed consistently increased global connectivity of the limbic regions across the two SCD cohorts ( Jiang et al, 2023 ). The results showed significantly higher degree of connectivity values in the cingulate cortex, hippocampus, and amygdala in SCD in comparison with HC, which is frequently interpreted as a compensatory phenomenon ( Catani et al, 2013 ), suggesting that vulnerable brain regions aroused excessively increasing connectivity.…”

Single-value fMRI scores reflect both stage and risk across the Alzheimer’s disease continuum

“…On the other hand, the sample was ethnically and sociodemographically rather homogenous, most likely owing to our recruiting strategy via memory clinics and newspaper advertisements. Further studies are needed to assess the generalizability of our findings to individuals from different ethnic and cultural backgrounds 73,74 .…”

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications

“…It generally includes the amygdala, thalamus, hypothalamus, and hippocampus, as well as many functionally and anatomically related regions that are considered paralimbic structures, including the prefrontal-limbic system, anterior cingulate cortex, medial temporal lobe network, para hippocampal gyrus, olfactory lobe, and ventral tegmental area ( Onofrj et al, 2022 ). Considerable overlap of the limbic network with the DMN, SN, and CEN can be seen in the anatomical composition, and this overlap also reflects the functional associations between the networks ( Jiang X. et al, 2023 ). This contains most of the inflammation-involved brain regions, thus explaining the peripheral inflammation-mediated impairment of memory and learning, both of which are often used as important dimensions in evaluating cognition.…”